JP5802499B2 - Analysis equipment - Google Patents

Description

  The present invention relates to an analyzer. More specifically, the present invention relates to an analyzer that detects a component of a sample injected into a flow path by an optical technique.

  In recent years, analysis in the fields of chemistry, biochemistry, pharmacy, medicine, veterinary medicine such as gene analysis, clinical diagnosis, and drug screening has been performed using a microchip device (microfluidic device).

  An analysis method for analyzing the concentration or amount of a specific component contained in a sample includes a method having a separation step for separating the specific component from the sample and a detection step for detecting the separated specific component. For example, in an analysis method using capillary electrophoresis, an electrophoresis solution is filled in a separation channel of a microchip device, and a sample is introduced near one end of the separation channel. When a voltage is applied to both ends of the separation channel, an electroosmotic flow is generated in which the electrophoresis solution moves from the positive electrode side to the negative electrode side by electrophoresis. Further, when the voltage is applied, the specific component tends to move according to the electrophoretic mobility. Therefore, the specific component moves according to a velocity vector obtained by synthesizing the velocity vector of the electroosmotic flow and the velocity vector of movement by electrophoresis. This movement separates the specific component from the other components. By detecting the separated specific component by, for example, an optical method, the amount and concentration of the specific component can be analyzed.

  Patent Document 1 describes a small microchemical system that does not require optical axis alignment and has high measurement sensitivity. The microchemical system includes a plate-like member with a channel in which a sample in liquid is filled in a channel, an optical fiber with a lens, a light source unit that emits excitation light and irradiates detection light, and a detection device. The optical fiber with a lens includes a gradient index rod lens, an optical fiber having one end connected to the gradient index rod lens, the other end connected to the light source unit, and an FC connector in the middle. The FC connector includes an FC plug and an adapter for fixing the FC plug, and is joined by screwing the FC plug into the adapter.

  Patent Document 2 describes a thermal lens spectroscopic analysis system and a thermal lens signal correction method that can accurately measure a sample even if the thermal lens signal intensity changes due to a change in the external environment. The thermal lens spectroscopic analysis system includes a microchemical chip having a groove into which a sample in liquid is injected, and a thermal lens that collects excitation light and detection light propagated from the light source unit through the optical fiber to the liquid sample. A gradient index rod lens that generates a signal, and a photoelectric converter that detects the amounts of excitation light and detection light and thermal lens signal intensity. Then, the thermal lens signal intensity measurement value, (predetermined light amount of excitation light / measurement light amount of excitation light), and / or second ratio (predetermined light amount of detection light / measurement light amount of detection light) are integrated to add heat. Correct the measured value of the lens signal strength.

  Patent Document 3 describes an analyzer including an optical fiber that guides light from a light source to a microchip. In the analyzer, a ferrule that holds an end portion of an optical fiber for guiding light from a light source to a microchip is held so as to be movable in a vertical direction in a state of being biased by a coil spring in the holder, and is applied to the microchip. It is configured to be touched.

JP 2004-117302 A JP 2006-300721 A International Publication No. 2010/010904

  As in the prior art described above, many efforts have been made to improve detection accuracy such as a light irradiation position and light collection as a method of performing analysis by an optical method. However, although the thermal effect at the time of control on the light irradiation side is considered, the thermal effect at the time of control on the light receiving side is not considered.

  In electrophoretic separation, not only the thermal effects of light irradiation, but also the heat generated by applying a voltage to the microchip (both ends of the separation channel), the microchip device is deformed by heat, and the accuracy of the analysis is increased. There was a problem of lowering. In particular, in the case of a resin microchip device, deformation is likely to be a problem.

  Further, when the sample to be analyzed is blood, protein, or the like, there is a possibility that heat denaturation may occur. Furthermore, there is a possibility that the accuracy of analysis may be reduced due to the generation of bubbles in the separation channel of the microchip device due to the influence of heat.

  In order to suppress the influence of these heats, the microchip device may be controlled to be cooled. In this case, the cooling control increases the temperature gradient between the inside and the outer surface of the microchip device. In some cases, this deformation was promoted.

  Also, heat may be generated during the reagent reaction, and it may be necessary to cool it. Deformation of the microchip device occurs due to the heat generated by the reagent reaction. Further, when cooling control of the microchip is performed, the deformation of the microchip device is promoted by the temperature gradient between the heat generation portion and the cooling portion inside.

  In a measurement method using a reagent reaction, an analysis by an optical method may be performed while adjusting the temperature of the microchip device. For example, when an enzyme reagent is used, it is desirable to adjust the temperature of the microchip device to around 37 degrees Celsius, which is highly reactive. In this case, the deformation of the microchip device occurred in the process of raising the temperature from the initial temperature of the microchip (for example, room temperature, temperature around 20 degrees Celsius) to 37 degrees Celsius.

  As described above, there is a problem that when the temperature change occurs from the inside of the microchip device or from the outside regardless of cooling and heating, the microchip device is deformed due to the influence.

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an analyzer that can reduce the thermal effect and prevent a decrease in measurement accuracy.

A support member that supports one side of the microchip and dissipates heat from the microchip ;
A first light guide means that is in contact with the other surface of the microchip and irradiates light to the photometry unit;
A second light guiding means that is inserted into a penetrating portion formed in the support member and is brought into contact with a surface on one side of the microchip to receive light via the photometric portion;
First biasing means for biasing the first light guide means toward the microchip;
A second biasing means for biasing the second light guide means toward the microchip and having a biasing force smaller than that of the first biasing means;
It is characterized by providing.

Preferably, at least one of the first light guiding means and the second light guiding means may comprise an optical fiber.

Preferably, at least one of the first light guide unit and the second light guide unit includes any one of a lens, a filter, and a housing.

Preferably, at least one of the first biasing means and the second biasing means is characterized by an elastic member.

  More preferably, the elastic member includes a spring mechanism.

  Preferably, the light receiving means includes a photodiode.

  Preferably, the microchip includes a light transmissive member in which a flow path is formed, and the photometric unit is the flow path.

  More preferably, the microchip is formed of a resin.

  Preferably, the analysis is performed using at least one of the indexes of reflectance, transmittance, absorbance, fluorescence, and luminescence of optical analysis.

  According to the present invention, it is possible to reduce the influence of heat and prevent a decrease in measurement accuracy.

It is a schematic block diagram which shows an example of the analyzer which concerns on embodiment of this invention. It is a top view which shows an example of the microchip which concerns on embodiment. It is the YY sectional view taken on the line of FIG. 2A. It is the elements on larger scale which show an example of the analysis measurement part of the analyzer which concerns on embodiment. It is a schematic block diagram which shows an example of the light guide means of the detection part which concerns on embodiment. It is a schematic block diagram which shows another example of the light guide means which concerns on embodiment. It is a schematic block diagram which shows an example of the analysis measurement part of the analyzer which concerns on embodiment. It is a schematic block diagram which shows an example of the analysis measurement part of the analyzer which concerns on the modification 1 of embodiment. It is a schematic block diagram which shows an example of the analysis measurement part of the analyzer which concerns on the modification 2 of embodiment. It is a schematic block diagram which shows an example of the analysis measurement part of the analyzer which concerns on the modification 2 of embodiment. It is a schematic block diagram which shows an example of the analysis measurement part of the analyzer which concerns on the modification 3 of embodiment. It is a schematic block diagram which shows an example of the microchip of the analyzer which concerns on embodiment. It is a ZZ line sectional view of Drawing 9A.

(Embodiment)
FIG. 1 is a schematic configuration diagram of an analyzer according to an embodiment of the present invention. In the present embodiment, the analysis apparatus 1 performs analysis using capillary electrophoresis and detects it using an optical technique.

  The analysis apparatus 1 includes a liquid storage tank 11, a sample tank 12, a waste liquid tank 13, a dispensing unit 14, a microchip 20, electrodes 24 and 25, an analytical measurement unit 40 having a detection unit 30, a flow channel 51 to a flow channel 53, Three-way valves 55 and 56, a control unit 61 and a power supply unit 62 are provided. In the microchip 20, a separation channel 21, an introduction hole 22, and a discharge hole 23 (see FIG. 2A) are formed.

  The liquid storage tank 11 stores a liquid L, for example, an electrophoretic liquid, purified water, and a cleaning liquid. The electrophoresis solution is a liquid that functions as a buffer. For example, there is an aqueous solution of 100 mM malic acid-arginine buffer (pH 5.0) + 1.5% chondroitin sulfate C sodium.

  The sample tank 12 stores the sample liquid K. The sample liquid K is a sample containing a specific component for performing analysis by the analyzer 1. The sample liquid K is a liquid that has been processed into a state suitable for measurement, for example, diluted or mixed.

  The waste liquid tank 13 is for storing a used liquid. The dispensing unit 14 can inject the sample liquid K in the sample tank 12 into the separation channel 21 of the microchip 20.

  FIG. 2A is a plan view showing an example of the microchip shown in FIG. 2B is a cross-sectional view taken along line YY of FIG. 2A.

  The microchip 20 includes a separation flow path 21 composed of fine flow paths, and an introduction hole 22 and a discharge hole 23 for introducing and discharging a solution to and from the separation flow path 21. The microchip 20 is formed by joining two resin substrates that are light transmissive members. The microchip 20 is made of, for example, a resin such as an acrylic resin such as silicon resin or methyl methacrylate resin, a polystyrene resin, or a polycarbonate resin.

  The separation channel 21 of the microchip 20 is a place where analysis using capillary electrophoresis is performed. The cross section of the separation channel 21 is preferably a circle having a diameter of 25 to 100 μm or a rectangle having a side length of 25 to 100 μm. There is no limitation to this as long as the shape and size are suitable for performing capillary electrophoresis. In the present embodiment, the length of the separation channel 21 is about 30 mm, but is not limited thereto.

  The separation channel 21 communicates with the introduction hole 22 and the discharge hole 23. The introduction hole 22 is provided at one end of the separation channel 21 and is a portion into which the sample liquid K is introduced from the dispensing unit 14. In the present embodiment, in addition to the sample liquid K, the storage liquid L such as electrophoresis liquid, purified water, and cleaning liquid can be introduced from the introduction hole 22. The discharge hole 23 is provided at the other end of the separation channel 21 and is a portion from which the sample liquid K and the storage liquid L filled in the separation channel 21 are discharged.

  The separation channel 21 is provided with electrodes 24 and 25 at both ends thereof. In the present embodiment, the electrode 24 is exposed in the introduction hole 22, and the electrode 25 is exposed in the discharge hole 23.

  FIG. 3 is a partially enlarged view showing an example of an analysis measurement unit of the analysis apparatus according to the embodiment. FIG. 3 schematically shows a cross section taken along the line MM of FIG.

  The analysis measurement unit 40 includes a microchip 20, a detection unit 30, a microchip support base 41, and a shielding wall 42. It is preferable that the irradiation control unit 35 and the light receiving control unit 36 which are a part of the detection unit 30 are arranged in different spaces which are provided with a predetermined distance from the microchip 20 and separated by a light blocking member. . The irradiation control unit 35 and the light receiving control unit 36 may be provided separately as shown in FIG. 3, or may be integrally formed and provided as an irradiation / light receiving control unit.

  Specifically, for example, the microchip 20 is arranged inside the shielding wall 42, and the irradiation control unit 35 and the light receiving control unit 36 are designed to be arranged outside the shielding wall 42. The irradiation control unit 35 is connected to the irradiation light guide 31 via the optical fiber 33, and the light receiving light guide 32 is connected to the light reception control unit 36 via the optical fiber 34. As the optical fibers 33 and 34, for example, quartz glass optical fibers are used.

  FIG. 4A is a schematic configuration diagram illustrating an example of a light guide unit of the detection unit according to the embodiment. The irradiation light guide 31 includes a ferrule 31a, a holder 31b, a coil spring 31c, and a stopper 31d. The ferrule 31a is fixed to its end so as not to interfere with the light guide of the optical fiber 33. The ferrule 31a is made of ceramic such as zirconia, for example. The ferrule 31a of the irradiation light guide 31 and the optical fiber 33 are collectively referred to as light irradiation means.

  The stopper 31d of the irradiation light guide 31 is not fixed to the optical fiber 33 but slides in accordance with the expansion and contraction of the coil spring 31c. By fixing the stopper 31d, the ferrule 31a of the light guide 31 for irradiation can be slid with respect to the stopper 31d.

  For example, when the irradiation light guide unit 31 is in contact with the microchip 20, a force (force F1: see FIG. 5) that presses against the microchip 20 at the tip (ferrule 31a) of the irradiation light guide unit 31 may be applied. The stopper 31d of the irradiation light guide 31 is fixed to a part of the shielding wall 42 at a position where it can be formed. When the microchip 20 is placed in the analyzer 1, the coil spring 31 c receives a force in the contracting direction, and the restoring force (force F <b> 1) can be urged to the microchip 20.

  FIG. 4B is a schematic configuration diagram illustrating another example of the light guide unit according to the embodiment. In the light guide unit of FIG. 4B, the holder 31b of the irradiation light guide unit 31 shown in FIG. 4A also serves as a stopper 31d.

  The holder 31b of the irradiation light guide 31 is not fixed to the ferrule 31a and the optical fiber 33, but slides relative to the optical fiber 33 in accordance with the expansion and contraction of the coil spring 31c. By fixing the holder 31b, the ferrule 31a of the irradiation light guide 31 can be slid.

  For example, when the irradiation light guide unit 31 is in contact with the microchip 20, at the position where the force (force F1) that presses against the microchip 20 with the tip of the irradiation light guide unit 31 (ferrule 31a) can be urged. The holder 31 b of the irradiation light guide 31 is fixed to a part of the shielding wall 42. When the microchip 20 is placed in the analyzer 1, the coil spring 31 c receives a force in the contracting direction, and the restoring force (force F <b> 1) can be urged to the microchip 20.

  The irradiation light guide 31 may include a lens at the tip of the ferrule 31a. The irradiation light guide unit 31 may include either a filter or a housing in addition to the lens.

  4A and 4B also show the configuration of the light receiving light guide 32. FIG. The light receiving means is configured by combining the ferrule 32 a of the light receiving light guide 32 and the optical fiber 34.

  In the case where no pressure is applied to the microchip 20, the light receiving light guide 32 need not be provided with an urging means, and may be formed only of the ferrule 32a.

  The light receiving light guide 32 includes an urging unit when pressure is applied to the microchip 20. The elastic structure, which is an urging means, is basically the same as the irradiation light guide 31 and includes a spring mechanism having a coil spring 32c. The light receiving light guide 32 may include a lens at the tip of the ferrule 32a. Moreover, the light guide 32 for light reception may be configured to include either a filter or a housing in addition to the lens.

  3, 4 </ b> A, and 4 </ b> B, the case where the irradiation light guide unit 31 is provided at a position facing the microchip support base 41 with the microchip 20 interposed therebetween is described as an example. In this case, in this embodiment, the irradiating light guide 31 is provided with an urging means, and the light receiving light guide 32 has an urging means having a weaker force than the urging means provided in the irradiating light guide 31. It is preferable to provide.

  When the light guide 31 for irradiation and the light guide 32 for light reception are in opposite positions, that is, when the light guide 32 for light reception is provided at a position facing the microchip support base 41 with the microchip 20 in between, The light receiving light guide 32 facing the microchip support base 41 is provided with a biasing means. More preferably, the irradiation light guide unit 31 includes an urging unit having a weaker force than the light reception light guide unit 32. In any case, it is sufficient that the force can be applied in the direction in which the microchip 20 is pressed against the microchip support base 41 by using the light guide means at a position facing the microchip support base 41.

  When the analysis is performed by the analyzer 1, since electrophoresis is performed by applying a voltage to the electrodes 24 and 25 at both ends of the separation channel 21, the temperature of the microchip 20 itself rises. When the temperature of the microchip 20 rises, due to the temperature rise in the separation channel 21, the buffer solution exceeds a predetermined temperature and a cloud point is generated, or denaturation such as protein coagulation occurs when the measurement target is blood or the like. The measurement accuracy decreases because it adversely affects the measurement. In addition, micro deformation occurs in the microchip 20 itself, and the relative position of the light receiving and emitting elements, that is, the distance between the light guide 31 for irradiation and the light guide 32 for light reception fluctuates, and the measurement accuracy decreases.

  Therefore, it is desirable to moderate the temperature rise of the microchip 20 as much as possible and not to exceed a predetermined temperature as much as possible. The microchip support base 41 is formed of a member such as aluminum having high thermal conductivity so that heat can be easily radiated. Configure. Further, for example, a cooling control may be performed by providing a Peltier element, or the cooling control may be performed by air cooling by a fan motor.

  For example, a measurement method using an enzyme reaction reagent other than electrophoresis may be configured to perform temperature control near 37 degrees Celsius in order to eliminate the influence of the reagent reaction on environmental temperature. In some cases, cooling control is performed to suppress heat generation during the reagent reaction.

  That is, when the microchip 20 is measured, the temperature of the measurement cell or the capillary itself changes, and if the temperature change affects the measurement accuracy, or is controlled to a desired temperature for the purpose of suppressing the temperature change or the like. There is a case. In these cases, the inside and outside of the microchip 20 are deformed under the influence of temperature changes.

  When analyzing and measuring with the analyzer 1, the irradiation control unit 35 and the light receiving control unit 36 are operated and the detection unit 30 performs detection. At this time, since the irradiation control unit 35 and the light receiving control unit 36 generate heat, there is a thermal effect on the microchip 20.

  On the other hand, the irradiation control unit 35 and the light receiving control unit 36 are easily affected by heat. The characteristics of the light receiving element or the light emitting element and the characteristics of the control circuit that drives the light receiving element or the light emitting element are fluctuated by the thermal effect from the microchip itself or from the element for controlling the temperature of the microchip. Variations in quantity can cause measurement errors. In general, the amount of light to be irradiated can be corrected by monitoring the reference light, but the amount of light received by the measurement light itself cannot be corrected directly, which affects the measurement accuracy.

  Moreover, it may be influenced by the element for temperature control and the electrical noise emitted from the microchip itself. Further, the irradiation control unit 35 and the light receiving control unit 36 may be affected by noise.

  Therefore, the irradiation control unit 35 and the light receiving control unit 36 are separated from the microchip 20, the influence of heat from the irradiation control unit 35 and the light receiving control unit 36 to the microchip 20, and the irradiation from the microchip 20. It is preferable to reduce the influence of heat on the control unit 35 and the light receiving control unit 36.

  For example, a space surrounded by the shielding wall 42 is provided as an environment that is not easily affected by temperature from the outside, and the microchip 20 is provided in the space inside the shielding wall 42. Heat from the irradiation control unit 35 and the light receiving control unit 36 placed outside the shielding wall 42 is difficult to be transmitted to the microchip 20 placed inside the shielding wall 42, and the influence of the heat on the microchip 20 is affected. Can be prevented. Further, the shielding wall 42 can remove stray light during light irradiation / light reception. The shielding wall 42 not only suppresses the temperature rise of the microchip 20 and reduces the influence on the measurement, but also has an effect of improving the measurement accuracy by removing the stray light.

  Further, for example, the irradiation control unit 35 and the light receiving control unit 36 are connected to the irradiation light guide 31 and the light receiving light guide 32 via the optical fibers 33 and 34. By using light guiding means such as optical fibers 33 and 34, the irradiation control unit 35 and the light receiving control unit 36, and the irradiation light guiding unit 31 and the light receiving light guiding unit 32 are arranged at a distance. And the influence of heat can be reduced. In addition, the use of the optical fibers 33 and 34 improves the workability when the microchip 20 is arranged at the analysis measurement location.

  The optical fiber 34 can be provided not only on the irradiation side but also on the light receiving side. For example, when a light receiving element of the light receiving control unit 36 uses a photodiode, the light receiving sensitivity of the photodiode has a temperature characteristic. Therefore, it is preferable that the light receiving light guide 32 has as little heat change as possible. When the optical fiber 34 on the light receiving side is not provided, the light receiving light guide portion 32 receives the heat generated by the light receiving control unit 36, changes in temperature, and the accuracy of light receiving measurement decreases. By providing the optical fiber 34, the influence of heat applied to the light guide 32 for light reception by the light reception control unit 36 can be reduced, so that the measurement accuracy can be prevented from being lowered.

  The analysis measurement unit 40 is preferably configured to dispose the electrodes 24 and 25 formed at both ends of the separation channel 21 outside the shielding wall 42. In addition to arranging the irradiation control unit 35 and the light receiving control unit 36 outside the shielding wall 42, the electrodes 24 and 25 are also arranged outside the shielding wall 42, so that the temperature inside the shielding wall 42 is further increased. And the temperature rise of the microchip 20 is reduced, and as a result, a decrease in measurement accuracy can be prevented.

  The detection unit 30 includes an irradiation light guide unit 31, a light reception light guide unit 32, optical fibers 33 and 34, an irradiation control unit 35, and a light reception control unit 36. The detection unit 30 is for analyzing a specific component separated from the sample liquid K in the separation channel 21. The irradiation light guide unit 31 and the light receiving light guide unit 32 of the detection unit 30 are provided in a portion of the separation channel 21 closer to the discharge hole 23 than the introduction hole 22.

  The irradiation light guide unit 31 is connected via an optical fiber 33 to an irradiation control unit 35 including a light source for irradiating light. For example, an LED or the like is used as the light source.

  The light receiving light guide 32 is connected to a light receiving control unit 36 having a light receiving part for receiving light through an optical fiber 34. For example, a photodiode or the like is used for the light receiving unit. The light receiving light guide 32 may further include a light collecting function such as a lens at the tip.

  The light guide 31 for irradiation and the light guide 32 for light reception are opposed to each other through the microchip 20, and the optical fibers 33 and 34 are arranged on the same axis. In order to improve the measurement accuracy, it is preferable that the deviation between the centers of the optical axes of the light guide 31 for irradiation and the light guide 32 for light reception is as small as possible.

  The control unit 35 for irradiation controls the light guide unit 31 for irradiation, and the control unit 36 for light reception controls the light guide unit 32 for light reception, so that the detection unit 30 samples the light from the light guide unit 31 for irradiation. The absorbance is measured by irradiating the liquid K and receiving the transmitted light by the light receiving light guide 32. Then, the calculation unit (not shown) of the control unit 61 calculates the extraction of the specific component and the concentration of the specific component from the absorbance, and the analysis process is completed. Hereafter, the effect | action in the analysis measurement of this Embodiment is demonstrated.

  FIG. 5 is a schematic configuration diagram illustrating an example of an analysis measurement unit of the analysis apparatus according to the embodiment. The microchip 20 is disposed in advance on the microchip support base 41 of the analysis measurement unit 40. Further, the irradiation light guide 31 and the light receiving light guide 32 are disposed so as to sandwich the separation channel 21 of the microchip 20. At this time, the irradiation light guide unit 31 applies a restoring force (force F1) of a predetermined force toward the microchip 20, and a force (force F1) that presses the microchip 20 against the microchip support base 41 acts.

  The irradiation light guide unit 31 is disposed between the introduction hole 22 and the discharge hole 23 at a position slightly beyond the discharge hole 23 when viewed in the flow direction of the flow path. The irradiation light guide unit 31 applies an urging force (force F <b> 1) so as to press the separation channel 21 of the microchip 20.

  In the analysis / measurement and detection process in the analyzer 1, the microchip 20 has the following influence. Since the analysis / measurement process is performed by electrophoresis, it is necessary to apply a voltage to the electrodes 24 and 25 at both ends of the separation channel 21. The temperature generated in the microchip 20 is caused by the current generated by the voltage. In the detection step, the light emitted from the light guide 31 for irradiation is received by the light guide 32 for light reception, and the separation channel 21 is irradiated with light in order to perform arithmetic processing. At this time, heat is generated by light irradiation, and the temperature of the microchip 20 rises.

  Due to the voltage application and the light irradiation, the temperature of the separation channel 21 of the microchip 20 rises, and the temperature rises more particularly in the vicinity of the photometric location. Since the microchip support base 41 is formed of a member such as aluminum having a high thermal conductivity and is configured to easily dissipate heat, compared to the surface of the microchip 20 on the side not facing the microchip support base 41, The surface on the side in contact with the microchip support base 41 is suppressed from rising in temperature. As a result, the surface of the microchip 20 on the side not facing the microchip support base 41 is easily affected by the temperature rise, and thermal expansion occurs in the microchip 20, and the microchip 20 is placed on the irradiation light guide 31 side. Deforms in a convex shape.

  At this time, the irradiation light guide unit 31 is in contact with the microchip 20 and is biased to the microchip 20 by a predetermined force (force F1) by the restoring force of the coil spring 31c, so that the microchip 20 becomes convex. Preventing deformation. The deformation of the separation channel 21 is suppressed by preventing the microchip 20 from being deformed into a convex shape. The deformation of the separation channel can be prevented, and the change of flow characteristics and the change of the light transmission direction can be prevented. As a result, the measurement accuracy can be prevented from being lowered. In addition, the irradiation light guide unit 31 and the microchip 20 can be kept in contact with each other, the light irradiation position is constant, and the optical distance in measurement is constant, so that a decrease in measurement accuracy can be suppressed. .

  Since the irradiating light guide unit 31 can apply a biasing force to the microchip 20 to prevent the microchip 20 from being deformed, the microchip 20 that is easily deformed by heat can be used. The microchip 20 may be made of not only glass but also resin such as acrylic resin such as silicon resin and methyl methacrylate resin, polystyrene resin and polycarbonate resin. Further, even for a material that is small in strength and easily deformed, the irradiation light guide unit 31 can apply a predetermined biasing force to the microchip 20 to prevent the deformation of the microchip 20. It can be used as a material.

  Hereinafter, with reference to FIG. 1 to FIG. 5, an operation of analyzing using the analyzer 1 will be described.

  The operation of each of the above-described units of the analyzer 1 is controlled by the control unit 61. Analysis by the analyzer 1 is performed by a series of controls. The control unit 61 is configured by, for example, a CPU, a memory, an input / output interface, and the like.

  The analysis apparatus 1 is provided with three-way valves 55 and 56. The three-way valves 55 and 56 each have three connection ports, and the connection state and the cutoff state of these connection ports are independently controlled by the control unit 61.

  The liquid storage tank 11 and the sample tank 12 are connected to the flow path 51 or the flow path 53 via three-way valves 55 and 56. Opening and closing is controlled by the control unit 61, and a communication state and a blocking state with the separation channel 21 are independently controlled. The channel 51 is connected to the microchip 20, that is, the separation channel 21, and the channel 53 is connected to the waste liquid tank 13.

  The power supply unit 62 is for applying a voltage for performing analysis by capillary electrophoresis in the separation channel 21 and is connected to the electrode 24 as a positive electrode and the electrode 25 as a negative electrode. The applied voltage is, for example, about 1.5 kV, and the positive electrode and the negative electrode may have a function of applying opposite polarities.

  Specifically, the separation by electrophoresis applies a voltage from the power supply unit 62 to the electrode 24 serving as the positive electrode and the electrode 25 serving as the negative electrode according to an instruction from the control unit 61, and travels from the electrode 24 to the electrode 25 to the electrophoresis solution. Generate electroosmotic flow. At this time, the specific component moves from the electrode 24 toward the electrode 25 in accordance with the inherent electrophoretic mobility.

  According to an instruction from the control unit 61, the analysis measurement unit 40 emits light from a light source from, for example, the irradiation light guide unit 31 at a specific position of the separation channel 21, and transmits the transmitted light by the light reception light guide unit 32. Receive light. More specifically, light having a wavelength of around 415 nm is irradiated from a light source 31 for irradiation from a light source such as an LED provided in the irradiation control unit 35 through the optical fiber 33, and the light transmitted through the light guide unit for light reception. The light is received by a light receiving unit such as a photodiode provided in the light receiving control unit 36 from the optical fiber 34 through the optical fiber 34. When a specific component passes through a specific position of the separation channel 21, the light (absorbance) received by the light receiving unit changes, and the concentration and amount of the specific component can be detected from the change.

  Heat is applied to the microchip 20 by applying a voltage to the separation channel 21 for electrophoresis and irradiating light for measurement, and the microchip 20 deforms due to temperature rise. Since the microchip support base 41 is formed of a member such as aluminum having a high thermal conductivity and is configured to easily dissipate heat, compared to the surface of the microchip 20 on the side not facing the microchip support base 41, The surface on the side in contact with the microchip support base 41 is suppressed from rising in temperature. As a result, the surface of the microchip 20 on the side not facing the microchip support base 41 is easily affected by the temperature rise, and thermal expansion occurs in the microchip 20, and the microchip 20 is placed on the irradiation light guide 31 side. Deforms in a convex shape.

  When the irradiation light guide unit 31 emits light for measurement, the irradiation light guide unit 31 is in contact with the microchip 20 and presses the microchip 20 so that the irradiation light guide unit 31 is in force. Light is irradiated while urging the microchip 20 with F1. More specifically, the coil spring 31c is compressed by the stopper 31d fixed to the shielding wall 42. Due to the restoring force, the ferrule 31a at the tip of the irradiation light guide 31 is biased to the microchip 20 by the force F1, and the separation channel 21 above the measurement location of the microchip 20 is moved in the direction of the microchip support base 41. Can be pressed.

  The microchip 20 receives an urging force (force F1) in a direction to return the portion deformed into a convex shape, and can prevent the microchip 20 from being deformed. Since the separation channel 21 does not need to be deformed, a change in flow characteristics in the separation channel 21 and a change in the light transmission direction such as irradiation caused by the deformation are prevented. As a result, the measurement accuracy is improved. A decrease can be prevented. In addition, the irradiation light guide unit 31 and the microchip 20 can be kept in contact with each other, the light irradiation position is constant, and the optical distance in measurement is constant, so that a decrease in measurement accuracy can be suppressed. .

  Further, the microchip 20 is placed inside the shielding wall 42 and is not affected by heat from the irradiation control unit 35 and the light receiving control unit 36. As a result, an increase in temperature of the microchip 20 can be reduced, and a reduction in measurement accuracy is prevented. Further, the presence of the shielding wall 42 improves the stray light removal effect in the analysis measurement unit 40 and contributes to improvement in measurement accuracy.

  Further, the light guide 32 for light reception and the control unit 36 for light reception are connected by an optical fiber 34, and a distance is provided between the light guide 32 for light reception and the control unit 36 for light reception. Is not affected by heat from the light receiving control unit 36. As a result, even if the light receiving light guide portion 32 is a member such as a photodiode whose light receiving sensitivity changes depending on the temperature, it is possible to prevent a decrease in measurement accuracy.

  The analysis result is completed by storing the analysis result in a storage unit (not shown), for example. The analysis using the analyzer 1 is completed through the above steps.

  FIG. 6 is a schematic configuration diagram illustrating an example of an analysis measurement unit of the analyzer according to the first modification of the embodiment. The basic structure is the same as that of the analyzer 1 according to the embodiment, and the light guide 32 for light reception can be energized like the light guide 31 for irradiation. The thing with small force urged | biased from the optical part 31 is used.

  Due to the voltage application and the light irradiation, the temperature of the separation channel 21 of the microchip 20 rises, and the temperature rises more particularly in the vicinity of the photometric location. Since the microchip support base 41 is formed of a member such as aluminum having a high thermal conductivity and is configured to easily dissipate heat, compared to the surface of the microchip 20 on the side not facing the microchip support base 41, The surface on the side in contact with the microchip support base 41 is suppressed from rising in temperature. As a result, the surface of the microchip 20 on the side not facing the microchip support base 41 is easily affected by the temperature rise, and thermal expansion occurs in the microchip 20, and the microchip 20 is placed on the irradiation light guide 31 side. Deforms in a convex shape.

  At this time, the irradiation light guide 31 is urged toward the microchip 20 with a predetermined force (force F1), urges the microchip 20 to be pressed against the microchip support base 41, and is deformed into a convex shape. To prevent. At the same time, the light receiving light guide 32 urges a predetermined force (force F2) toward the irradiation light guide 31, that is, from the light receiving light guide 32 toward the microchip 20.

  By providing the light receiving light guide portion 32 with a function of urging a spring or the like, the light receiving portion 32 can be pressed so as to sandwich the separation channel 21 of the microchip 20. As a result, the irradiation light guide unit 31 and the microchip 20 come into contact with each other, and the light receiving light guide unit 32 and the microchip 20 facing the irradiation light guide unit 31 come into contact with each other. The irradiation light guide 31, the light reception light guide 32, and the microchip 20 are integrated, and the positional relationship (optical distance) is constant, so that a reduction in measurement accuracy can be suppressed.

  Even if the convex deformation generated in the microchip 20 cannot be suppressed by the force (force F1) urging the irradiation light guide unit 31 and a slight convex deformation occurs in the microchip 20, Since a predetermined force (force F2) is urged from the light receiving light guide 32 to the microchip 20, the irradiation light guide 31, the light receiving light guide 32, and the microchip 20 remain integrated with each other. Can be maintained. As a result, since the positional relationship (optical distance) is constant, a decrease in measurement accuracy can be suppressed.

  Note that the case where the force (force F <b> 2) energized by the light receiving light guide 32 is not energized is equal to the case of the above-described embodiment (see FIG. 5).

  7A and 7B are schematic configuration diagrams illustrating an example of an analysis measurement unit of the analysis apparatus according to the second modification of the embodiment. The basic structure is the same as that of the analyzer 1 according to the embodiment, and the positions of the light guide 31 for irradiation and the light guide 32 for light reception are inverted up and down. Specifically, the light receiving light guide 32 is provided at a position facing the microchip support base 41 with the microchip 20 interposed therebetween, and the irradiation light guide 31 is provided at a position on the microchip support base 41 side. It is done. 7A corresponds to FIG. 5, and FIG. 7B corresponds to FIG.

  In the present embodiment, as shown in FIG. 7A, it is necessary to provide an urging means for urging the microchip 20 toward the microchip support base 41. At least the light receiving light guide 32 includes a biasing unit that biases the microchip 20 with a predetermined force (force F2).

  Further, as shown in FIG. 7B, when the urging means is provided not only for the light receiving light guide 32 but also for the irradiation light guide 31, the urging force (force F1) of the irradiation light guide 31 is for light reception. An urging means is provided so as to be smaller than the force (force F2) urged by the light guide unit 32. The microchip 20 is urged to the microchip support 41 by making the force (force F2) urging the light receiving light guide portion 32 larger than the force (force F1) urging the irradiation light guide portion 31. can do.

  FIG. 8 is a schematic configuration diagram illustrating an example of an analysis measurement unit of the analysis apparatus according to the third modification of the embodiment. The basic structure is the same as that of the analyzer 1 according to the embodiment, and is a case where the microchip presser 43 is additionally provided.

  For example, when the microchip 20 is insufficiently fixed to the microchip support base 41, the microchip 20 is formed of a lightweight member such as a resin and is not easily fixed to the microchip support base 41. Prepare for the case. In the present invention, a microchip presser 43 that can press the microchip 20 against the microchip support base 41 with a predetermined force (force F3) is used.

  The irradiation light guide unit 31 abuts on the microchip 20 and urges the microchip 20 toward the microchip support base 41 with a predetermined force (force F1), and the microchip presser 43 also has a predetermined force (force F3). Then, it is biased toward the microchip support base 41. As a result, even when convex deformation occurs in the microchip 20 at the time of analysis, the irradiation light guide unit 31 and the microchip presser 43 are energized to suppress the deformation. At this time, the predetermined force (force F <b> 1) when energizing with the irradiation light guide unit 31 may be smaller than when energizing only with the irradiation light guide unit 31.

  In the case where the light guide 32 for light reception is urged with a predetermined force (force F2), when the microchip presser 43 is not provided, the predetermined force (force F1) urged with the light guide 31 for irradiation is used. Must be greater than a predetermined force (force F2) urged by the light receiving light guide 32, but may be equivalent. With the microchip presser 43, the microchip 20 can be urged toward the microchip support base 41, and it is possible to suppress the convex deformation of the microchip 20. As a result, the deformation of the microchip 20 can be suppressed and the measurement accuracy can be prevented from being lowered. In addition, the light guide 31 for irradiation and the light guide 32 for light reception can be held so as to sandwich the microchip 20 (including the separation flow path 21 at the photometric location) between them, and the optical distance can be kept constant. , More accurate measurement can be performed.

  FIG. 9A is a schematic configuration diagram showing an example of a microchip of the analyzer according to the present embodiment. The microchip 20 includes a guide (concave portion) 26 on the upper part of the separation channel 21 where the detection unit 30 is provided. The guide 26 has a gap, and can fit the irradiation light guide 31.

  9B is a cross-sectional view taken along the line ZZ in FIG. 9A. The guide 26 is formed at a predetermined position on the separation channel 21 and can irradiate light to a predetermined position from the irradiation light guide 31 to the separation channel 21. As a result, it is possible to irradiate light to a predetermined position without positioning by simply fitting the light guide 31 for irradiation to the guide 26, and the microchip 20 can be easily disposed on the microchip support base 41. Is possible. In addition, since the position where light is irradiated is fixed, the optical distance in measurement is constant, and measurement can be performed stably.

  In addition, by using the microchip 20 provided with the guide 26, the contact pressure position is fixed when a force for urging the microchip 20 by the irradiation light guide unit 31 is applied. Can be added. By applying an addition to the microchip 20 with a certain force at a predetermined detection location, stable measurement, in this case, light irradiation and light reception can be performed.

  As described above, according to the analyzer according to the embodiment, it is possible to reduce the thermal effect and prevent the measurement accuracy from being lowered.

  In the detection of a specific component, when irradiating light to the separation channel of the microchip, the microchip and the separation channel can be deformed by heat by applying a force that directly urges the microchip using the light irradiation means. It is possible to prevent changes in flow characteristics in the separation channel and changes in the light transmission direction such as irradiation, and it is possible to prevent a decrease in measurement accuracy. Also, by applying a force that directly urges the microchip using the light irradiation means, the distance between the light guide means on both sides of the microchip can be kept constant, and the optical distance becomes constant and the measurement accuracy Suppresses the decline.

  Further, by arranging the light guiding means that contacts or is close to the microchip (separation flow path) and the light receiving control unit using an optical fiber, the light receiving unit such as a photodiode and the light receiving control unit are arranged. Can be kept away. As a result, it is possible to reduce the change in the light receiving sensitivity of the photodiode due to the temperature and prevent the measurement accuracy from being lowered.

  In addition, the light guide means that comes into contact with or close to the microchip (separation flow path) and the light irradiation / light reception control unit of the light guide means are provided separately to reduce the thermal effect on the microchip and buffer A decrease in measurement accuracy due to the cloud point of the liquid can be prevented. In addition, it is possible to reduce the denaturation of the sample that occurs at a predetermined temperature or higher, for example, the occurrence of protein coagulation at a high temperature, and to prevent a decrease in measurement accuracy.

  The analyzer according to the present embodiment is not limited to the example described above. The specific configuration of the analyzer according to the present invention can be varied in design in various ways. For example, the configuration of the flow path, the number of reservoirs, the position where each functional unit is arranged, the shape of each functional unit, and the like can be designed in accordance with the application of the analyzer. The analysis using the analyzer can be applied to an analysis using at least one of the reflectance, transmittance, absorbance, fluorescence, and luminescence of optical analysis.

  The example of deformation that occurs in the microchip described in this embodiment is an example. Depending on various factors such as the type of analysis apparatus, analysis method, analysis target, and microchip used, the shape, degree of deformation, and direction of deformation of the microchip vary. In the present embodiment, it is only necessary to use the light irradiation means and / or the light receiving means to urge the microchip to be pressed toward the support member and to suppress the deformation of the microchip. It is not limited. In addition, the magnitude of the biasing force also takes into account the material of the microchip, the analysis temperature, the difference between the biasing force of the light irradiation means and the biasing force of the light receiving means, and the direction of the biasing force. Can be set arbitrarily.

  The force urged by the light guide means used for analysis is not limited to a coil spring, and a leaf spring or other elastic body may be used. Further, the location where the light guiding means is arranged on the microchip (separation channel) is not limited to the above-described example. When arranging, it is preferable to arrange so that the concentricity of the optical axis between light irradiation and light reception is as small as possible.

  The microchip is not limited to resin but may be made of glass. Further, the number of separation channels provided in the microchip is not limited to one and may be plural. The configuration of the separation channel is not limited to a so-called straight shape, and may be a cross-injection shape in which two channels are toleranced.

1 Analyzer
11 Liquid storage tank
12 Sample tank
13 Waste liquid tank
14 Dispensing part
20 microchip
21 Separation channel
22 Introduction hole
23 Discharge hole 24, 25 Electrode
26 Guide (recess)
30 detector
31 Irradiation light guide 31a, 32a Ferrule 31b, 32b Holder 31c, 32c Coil spring 31d, 32d Stopper
32 Light-receiving portion for light reception 33, 34 Optical fiber
35 Irradiation control unit
36 Control unit for light reception
40 Analysis measurement unit
41 Microchip support
42 Shielding wall
43 Microchip retainer 51-53 Flow path 55, 56 Three-way valve
61 Control unit
62 Power supply
L liquid storage
K sample solution

Claims (10)

A microchip having a photometric unit;
A support member that supports one side of the microchip and dissipates heat from the microchip ;
A first light guide means that is in contact with the other surface of the microchip and irradiates light to the photometry unit;
A second light guiding means that is inserted into a penetrating portion formed in the support member and is brought into contact with a surface on one side of the microchip to receive light via the photometric portion;
First biasing means for biasing the first light guide means toward the microchip;
A second biasing means for biasing the second light guide means toward the microchip and having a biasing force smaller than that of the first biasing means;
An analysis apparatus comprising: A microchip having a photometric unit;
A support member that supports one side of the microchip and dissipates heat from the microchip;
A first light guiding means that is inserted into a penetrating portion formed in the support member and is brought into contact with a surface on one side of the microchip, and irradiates light to the photometric portion;
A second light guide means which is in contact with the other surface of the microchip and receives light via the photometry unit;
First biasing means for biasing the first light guide means toward the microchip;
Urging the second light guide means toward the microchip, and a second urging means having a larger urging force than the first urging means;
An analysis apparatus comprising: The analyzer according to claim 1 or 2, wherein at least one of the first light guide unit and the second light guide unit includes an optical fiber. 3. The analyzer according to claim 1, wherein at least one of the first light guide unit and the second light guide unit includes a lens, a filter, or a housing. 5. The analyzer according to claim 1, wherein at least one of the first urging unit and the second urging unit includes an elastic member. The analyzer according to claim 5, wherein the elastic member includes a spring mechanism. The second light guiding means is connected to a light receiving control unit,
The analyzer according to claim 1, wherein the light receiving control unit includes a photodiode. The analyzer according to any one of claims 1 to 7, wherein the microchip includes a light-transmitting member in which a channel is formed, and the photometric unit is the channel. The analyzer according to claim 8, wherein the microchip is made of a resin. The analysis apparatus according to any one of claims 1 to 9, wherein the analysis is performed using at least any one of an index among reflectance, transmittance, absorbance, fluorescence, and light emission of optical analysis.

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